This study was aimed at the elucidation of mechanisms and the identification of early parameters of immune dysfunction in SIV induced primate AIDS. The results obtained on disease susceptible rhesus macaques experimentally with SIVmac251 were compared to parameters derived from naturally infected disease resistant sooty mangabey monkeys. A total of 9 macaques were immunized with keyhole limpet hemocyanin (KLH), tetanus toxoid (TT) and the highly attenuated influenza virus strain A/PR8 prior to challenge with SIVmac251 (6 out of the 9 macaques). Immune responses not only to SIV but also to KLH, TT and influenza were followed throughout the course of infection in order to identify the onset of critical immune dysfunctions following SIV infection. The results of these studies suggest that a rapid loss of antigen specific IFN-( response is observed in all SIV infected macaques accompanied with a gradual increase in IL-6 responses as the monkeys reach the clinically sym ptomatic stage. Humoral responses established prior to SIV infection did not seem to be affected when compared to uninfected control animals. However, the kinetic of cell mediated response to influenza and the capacity of the animal's PBMC to synthesize IL-2 in response to antigenic stimulation in vitro appeared to correlate with the length of time between infection with SIV and development of AIDS, suggesting a preponderant role for these mechanisms at maintaining the clinical status quo following lentiviral infection. FUNDING NIH / NIAID $231,478 9/30/97 - 8/31/01 PUBLICATIONS Courgnaud, V., Saurin, W., Villinger, F. and Sonigo, P. Evolution differences of simian immunodeficiency virus in a natural host and a new host. Virology 247:41-50, 1998. Smit-McBride, Z., Mattapallil, J, Villinger, F., Ansari, A.A. and Dandekar, S. Intracellular cytokine expression in the CD4+ and CD8+ T cells from intestinal mucosa of simian immunodeficiency virus infected macaques. J Med Primatol 27:129-140, 1998. Villinger, F., Brice, G.T., Mayne, A., Bostik, P. and Ansari, A.A. Control mechanisms of virus replication in naturally SIVsmm infected mangabeys and experimentally infected macaques. Immunol Lett 51(1-2):59-68, 1998. P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center